Association of Clonal Hematopoiesis of Indeterminate Potential with Inflammatory Gene Expression in Patients with COPD

Kuhnert, Stefan; Mansouri, Siavash; Rieger, Michael A.; Savai, Rajkumar; Avci, Ercan; Díaz-Piña, Gabriela; Padmasekar, Manju; Looso, Mario; Hadžić, Stefan; Acker, Till; Klatt, Stephan; Wilhelm, Jochen; Fleming, Ingrid; Sommer, Natascha; Weißmann, Norbert; Vogelmeier, Claus; Bals, Robert; Zeiher, Andreas M.; Dimmeler, Stefanie; Seeger, Werner; Pullamsetti, Soni Savai

doi:10.3390/cells11132121

Cited by 9 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is noteworthy to highlight an age-associated phenomenon known as clonal haematopoiesis of indeterminate potential (CHIP) [ 162 ]. The aggregation of sets of somatic mutations in haematopoietic stem cells over the course of a human lifespan represents a distinctly delineated phenomenon that becomes increasingly evident with advancing age [ 163 , 164 ].…”

Section: The Aged Macrophagementioning

confidence: 99%

“…This phenomenon has been identified as a contributor to inflammation and, given the continuous exchange of TR-AMs by BMDMs, may significantly affect lung health and disease in the aged. CHIP contributes to the altered inflammatory response seen in chronic diseases related to inflammatory macrophage phenotypes, including cardiovascular disease [ 165 ], COPD, IPF [ 162 , 166 , 167 ] and atherosclerosis [ 168 ]. The findings indicate an augmented risk of both the incidence and severity of COPD in patients exhibiting CHIP, thereby emphasising the potential clinical implications.…”

Section: The Aged Macrophagementioning

confidence: 99%

See 1 more Smart Citation

The guardians of pulmonary harmony: alveolar macrophages orchestrating the symphony of lung inflammation and tissue homeostasis

Pervizaj-Oruqaj,

Ferrero,

Matt

et al. 2024

Eur Respir Rev

View full text Add to dashboard Cite

Recent breakthroughs in single-cell sequencing, advancements in cellular and tissue imaging techniques, innovations in cell lineage tracing, and insights into the epigenome collectively illuminate the enigmatic landscape of alveolar macrophages in the lung under homeostasis and disease conditions. Our current knowledge reveals the cellular and functional diversity of alveolar macrophages within the respiratory system, emphasising their remarkable adaptability. By synthesising insights from classical cell and developmental biology studies, we provide a comprehensive perspective on alveolar macrophage functional plasticity. This includes an examination of their ontology-related features, their role in maintaining tissue homeostasis under steady-state conditions and the distinct contribution of bone marrow-derived macrophages (BMDMs) in promoting tissue regeneration and restoring respiratory system homeostasis in response to injuries. Elucidating the signalling pathways within inflammatory conditions, the impact of various triggers on tissue-resident alveolar macrophages (TR-AMs), as well as the recruitment and polarisation of macrophages originating from the bone marrow, presents an opportunity to propose innovative therapeutic approaches aimed at modulating the equilibrium between phenotypes to induce programmes associated with a pro-regenerative or homeostasis phenotype of BMDMs or TR-AMs. This, in turn, can lead to the amelioration of disease outcomes and the attenuation of detrimental inflammation. This review comprehensively addresses the pivotal role of macrophages in the orchestration of inflammation and resolution phases after lung injury, as well as ageing-related shifts and the influence of clonal haematopoiesis of indeterminate potential mutations on alveolar macrophages, exploring altered signalling pathways and transcriptional profiles, with implications for respiratory homeostasis.

show abstract

Section: The Aged Macrophagementioning

confidence: 99%

Section: The Aged Macrophagementioning

confidence: 99%

The guardians of pulmonary harmony: alveolar macrophages orchestrating the symphony of lung inflammation and tissue homeostasis

Pervizaj-Oruqaj,

Ferrero,

Matt

et al. 2024

Eur Respir Rev

View full text Add to dashboard Cite

show abstract

“…GWAS and candidate gene approaches have previously been used to identify mechanisms of germline predisposition to viral, bacterial, and parasitic infections common to the ICU (70, 71). The potential applicability of somatic CH variants to critical illness is highlighted by preliminary observations that they increase risks of pulmonary disease (33, 72), kidney disease (32), and cardiogenic shock (73). Further evidence suggests that CH predisposes to diverse types of severe infection.…”

Section: Clinical Significance and Conclusionmentioning

confidence: 99%

COVID-19 and the Genetics of Inflammation

Choudhri

Maslove

Rauh

2023

Critical Care Medicine

View full text Add to dashboard Cite

COVID-19 and the Genetics of InflammationOBJECTIVE: Interindividual variability in the clinical progression of COVID-19 may be explained by host genetics. Emerging literature supports a potential inherited predisposition to severe forms of COVID-19. Demographic and inflammatory characteristics of COVID-19 suggest that acquired hematologic mutations leading to clonal hematopoiesis (CH) may further increase vulnerability to adverse sequelae. This review summarizes the available literature examining genetic predispositions to severe COVID-19 and describes how these findings could eventually be used to improve its clinical management.DATA SOURCES: A PubMed literature search was performed. STUDY SELECTION:Studies examining the significance of inherited genetic variation or acquired CH mutations in severe COVID-19 were selected for inclusion. DATA EXTRACTION:Relevant genetic association data and aspects of study design were qualitatively assessed and narratively synthesized.DATA SYNTHESIS: Genetic variants affecting inflammatory responses may increase susceptibility to severe COVID-19. Genome-wide association studies and candidate gene approaches have identified a list of inherited mutations, which likely alter cytokine and interferon secretion, and lung-specific mechanisms of immunity in COVID-19. The potential role of CH in COVID-19 is more uncertain at present; however, the available evidence suggests that the various types of acquired mutations and their differential influence on immune cell function must be carefully considered. CONCLUSIONS:The current literature supports the hypothesis that host genetic factors affect vulnerability to severe COVID-19. Further research is required to confirm the full scope of relevant variants and the causal mechanisms underlying these associations. Clinical approaches, which consider the genetic basis of interindividual variability in COVID-19 and potentially other causes of critical illness, could optimize hospital resource allocation, predict responsiveness to treatment, identify more efficacious drug targets, and ultimately improve outcomes.

show abstract

“…Wir konnten in einer kleinen Kohorte von Patient*innen mit COPD von unterschiedlichem Schweregrad die hohe Inzidenz von CHIP bestätigen, wobei auch in unserer Kohorte DNMT3A das mit Abstand am häufigsten betroffene Gen war [ 44 ]. Da CHIP-Treibermutationen in DNMT3A meist zu einem Funktionsverlust führen, zeigte die genetische Abschaltung von DNMT3A in Makrophagen eine gesteigerte Produktion von IL‑6 und Tumor-Nekrose-Faktor α und eine globale Hypomethylierung im Genom.…”

Section: Weitere Nicht-hämatologische Erkrankungen Unter Dem Einfluss...unclassified

“…Betroffen waren dabei interessanterweise keine Gene, die für Zytokine und Chemokine codieren, sondern solche für metabolische Regulatoren, wie „phospholipase D family member 5“ (PLD5). Die PLD5-Expression korrelierte mit gesteigertem Glycerophosphocholin, proinflammatorischen Zytokinen und reduzierter Lungenfunktion bei Patient*innen mit COPD [ 44 ].…”

Section: Weitere Nicht-hämatologische Erkrankungen Unter Dem Einfluss...unclassified

Einfluss der klonalen Hämatopoese auf nicht-hämatologische Erkrankungen und Alterungsprozesse

Rieger

2022

Innere Medizin

Self Cite

View full text Add to dashboard Cite

Das Auftreten von klonaler Hämatopoese, ausgelöst durch erworbene somatische Mutationen in leukämieassoziierten Genen in Blutstammzellen, ist weit verbreitet und steigt mit zunehmendem Alter. Neben einem erhöhten Risiko, eine myeloische Neoplasie zu entwickeln, wurde in den letzten Jahren ein unerwarteter, kausaler Zusammenhang zwischen klonaler Hämatopoese und Herz-Kreislauf-Erkrankungen gefunden. Klonale Hämatopoese präsentiert sich als neuer, unabhängiger und hoher Risikofaktor für kardiovaskuläre Erkrankungen wie Atherosklerose, koronare Herzkrankheit, Herzinsuffizienz, Aortenklappenstenose sowie Schlaganfall und sollte aus medizinischer Sicht nicht mehr ignoriert werden. Die weltweit intensive Forschung nach Assoziationen von klonaler Hämatopoese mit anderen altersbedingten Leiden und mit Infektionskrankheiten findet immer mehr Erkrankungen, die durch die Anwesenheit mutierter Blutzellen beeinflusst werden. Aktuelle Erkenntnisse beschreiben einen fatalen Kreislauf, der ausgelöst durch somatische Blutzellmutationen den Krankheitsverlauf assoziierter Erkrankungen proinflammatorisch verstärkt und sich auf eine Vergrößerung des mutierten Blutzellklons auswirkt. Erste experimentelle Therapieansätze, um diesen Teufelskreis zu brechen, werden hier diskutiert. Die kausalen Zusammenhänge und Pathomechanismen stehen jetzt im Zentrum der Forschung, um Risikoabschätzungen und therapeutische Maßnahmen zum Wohle der Patient*innen rasch auf den Weg bringen zu können.

show abstract

Association of Clonal Hematopoiesis of Indeterminate Potential with Inflammatory Gene Expression in Patients with COPD

Cited by 9 publications

References 18 publications

The guardians of pulmonary harmony: alveolar macrophages orchestrating the symphony of lung inflammation and tissue homeostasis

The guardians of pulmonary harmony: alveolar macrophages orchestrating the symphony of lung inflammation and tissue homeostasis

COVID-19 and the Genetics of Inflammation

Einfluss der klonalen Hämatopoese auf nicht-hämatologische Erkrankungen und Alterungsprozesse

Contact Info

Product

Resources

About